The purpose of this work is to elucidate the principles of treatment of chronic pain syndromes that are considered resistant to conventional treatment, such as pain caused by nerve injury and by advanced cancer. There is a particular emphasis on pain caused by peripheral neuropathies. Such as syndrome occurs in about 5% of patients with AIDS. We focus on pain in patients with painful neuropathy and post-herpetic neuralgia. A study showing amitriptyline to relieve diabetic neuropathy pain in both depressed and non-depressed patients was completed. Thirty-eight of a projected 40 patients with postherpetic neuralgia have completed a crossover study of amitriptyline, lorazepam, and placebo. An interim analysis at n=29 showed a trend towards relief with amitriptyline. Two further studies examining the mechanism of relief of neuropathic pain by antidepressants will begin soon. Amitriptyline potentiates the action of both serotonin and norepinephrine at central synapses. We will examine fluoxetine which is specific for serotonin, and desipramine, which is relatively specific for norepinephrine. We will also collaborate with CC Anesthesiology and NHLBI in a study of catecholamine kinetics in the vascular system of patients with reflex sympathetic dystrophy, to see how alterations in catecholamine release affect their pain.